Rat corneal allograft survival prolonged by the superantigen staphylococcal enterotoxin B.

Abstract

The purpose of this study was to determine the optimal conditions for prolonging corneal allograft survival by inducing anergy with the superantigen staphylococcal enterotoxin B (SEB). A rat model of penetrating keratoplasty, whereby Fisher344 donor corneas are implanted into Lewis recipients, was used to evaluate the effects of SEB on inhibiting immune-mediated allograft rejection. To induce anergy, SEB was injected into the peribulbar space of Lewis rats. Furthermore, histopathology and immunofluorescent staining were used to examine the levels of infiltrating CD4(+) and CD8(+) T lymphocytes and NK1.1(+) lymphocytes. By administering SEB, at doses of 90 or 120 micro g/kg 7 days before and after keratoplasty, we suppressed the episode of corneal graft rejection for a median of 12 and 30 days, respectively. In contrast, rejection was observed when 30 or 60 micro g/kg of SEB was administered. After SEB injections, lymphocyte infiltration into the corneal grafts was reduced, and the expression of NK1.1(+) lymphocytes was enhanced, suggesting that anergy may be occurring. Also, there were no differences in the number of infiltrating CD4(+) and CD8(+) T lymphocytes cells between the control group and groups injected with 30 and 120 micro g/kg SEB on postoperative days 10 and 30. Inducing anergy with the superantigen SEB prolonged corneal graft survival in a rat model of penetrating keratoplasty. Therefore, these results support the possibility of prolonging corneal allograft survival in a clinical setting by preventing immune-mediated rejection through the administration of the superantigen SEB.